1.14.18.6: 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase
This is an abbreviated version!
For detailed information about 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase, go to the full flat file.
Word Map on EC 1.14.18.6
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1.14.18.6
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paraplegia
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sphingolipids
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2-hydroxylation
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leukodystrophy
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nbias
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atp13a2
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dystonia
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pla2g6
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paraparesis
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galactosylceramide
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sulfatide
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alpha-hydroxylation
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paucimobilis
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hydroxylase-associated
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medicine
- 1.14.18.6
- paraplegia
- sphingolipids
-
2-hydroxylation
- leukodystrophy
- nbias
-
atp13a2
- dystonia
- pla2g6
- paraparesis
- galactosylceramide
- sulfatide
-
alpha-hydroxylation
- paucimobilis
-
hydroxylase-associated
- medicine
Reaction
Synonyms
FA2H, AtFAH1, FA2H, FAH1, fatty acid 2-hydroxylase, fatty acid 2-hydroxylase 1, fatty acid alpha-hydroxylase, SCS7, Scs7p, scScs7p, sphingolipid alpha-hydroxylase
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1.14.18.6 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylaseAdvanced search results
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results (General Information
General Information on EC 1.14.18.6 - 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
FA2H/Scs7p belongs to a superfamily of integral membrane di-iron-containing enzymes that hydroxylate or desaturate lipid-based substrates via a reaction mechanism that is dependent on NADH and oxygen
physiological function
additional information
physiological function
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a yeast strain that lacks the FAH1 gene is resistant to antifungal cyclic lipodepsinonapeptide syringomycin E
physiological function
COS7 cells expressing human FA2H contain 3-20fold higher levels of 2-hydroxyceramides (C16, C18, C24, and C24:1) and 2-hydroxy fatty acids compared with control cells
physiological function
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Deletion of hydroxylase scs7 causes synthetic lethality in combination deletion of phosphoinositide phosphatase SAC1. Overexpression of PSS1 encoding phosphatidylserine synthase complements the growth defects of scs7 deletion cells under SAC1-repressive conditions, and overexpression of Arf-GAP AGE1, which encodes aprotein related to membrane trafficking, also complements
physiological function
disruption of the FAH1 gene does not give any visible phenotype, and there is no observable difference in content or distribution of the most abundant long chain saturated and unsaturated 14-18-carbon fatty acid species. The gene-disrupted DELTAfah1 strain shows an approximately 40fold reduction of alpha-hydroxy-fatty acid 26:0 and a complementary increase in fatty acid 26:0. Expression of Arabidopsis thaliana FAH1 gene, which does not contain the cytochrome b5 domain, in the Saccharomyces cerevisiae DELTAfah1 strain produces an approximately 25fold increase in alpha-hydroxyfatty acid 26:0 and reduces the levels of its 26-carbon precursor
physiological function
FA2H knockdown in adipocytes increases diffusional mobility of raft-associated lipids, leading to reduced GLUT4 protein level, glucose uptake, and lipogenesis
physiological function
FA2H-siRNA suppresses 2-hydroxylase activity and decreases 2-hydroxyceramide/2-hydroxyglucosylceramide levels. Keratinocytes transduced with FA2H-siRNA contain abnormal epidermal lamellar bodies and do not form the normal extracellular lamellar membranes required for the epidermal permeability barrier
physiological function
fatty acid 2-hydroxylase Fa2h/UDP-galactose:ceramide galactosyltransferase Cgt double-deficient mice lack sulfatide, GalCer, and in addition 2-hydroxylated fatty acid-galactosylceramide and sphingomyelin. Compared to Cgt-/- mice the amount of GlcCer in central nervous system myelin is strongly reduced in Fa2h-/-/Cgt-/- mice by more than 80%. This is accompanied by a significant increase in sphingomyelin, which is the predominant sphingolipid in Fa2h-/-/Cgt-/- mice. Compact myelin is formed in Fa2h-/-/Cgt-/- mice, and g-ratios of myelinated axons in the spinal cord of 4-week-old Fa2h-/-/Cgt-/- mice do not differ significantly from that of Cgt-/- mice, and there is no obvious phenotypic difference between Fa2h-/-/Cgt-/- and Cgt-/- mice
physiological function
mutants lacking Scs7 fail to accumulate the inositolphosphorylceramide species, IPC-C, which is the predominant form found in wild-type cells. Instead scs7 mutants accumulate an IPC-B species believed to be unhydroxylated on the amide-linked C26-fatty acid. Elimination of the gene suppresses the Ca2+-sensitive phenotype of csg1 and csg2 mutants. The CSG1 and CSG2 genes are required for mannosylation of IPC-C
physiological function
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partial silencing of fatty acid 2-hydroxylase FA2H in D6P2T cells results in 60-70% reduction of hydroxyl fatty acid-dihydroceramide and hydroxyl fatty acid-ceramide, with no effect on nonhydroxy dihydroceramide and ceramide.Under these conditions, dibutyryl-cAMP no longer induces cell cycle exit, and cells continue to grow and divide. FA2H silencing prevents dibutyryl-cAMP-induced upregulation of cyclin-dependent kinase inhibitors p21 and p27
physiological function
silencing of sphingolipid fatty acyl 2-hydroxylase Fa2h turns the cells resistant to synthetic antitumor drug PM02734, i.e. elisidepsin. Overexpression of Fa2H leads to an increased sensitivity to PM02734
physiological function
silencing of sphingolipid fatty acyl 2-hydroxylase Scs7 turns the cells resistant to synthetic antitumor drug PM02734, i.e. elisidepsin. Overexpression of Scs7 renders the cells hypersensitive to PM02734
physiological function
transfection of FA2H cDNA in CHO cells leads to the formation of hexosylceramide containing alpha-hydroxylated fatty acid
physiological function
enzyme Scs7p is responsible for adding a hydroxyl group to the alpha-carbon of the VLCFA moiety of the ceramide substrate to generate inositol phosphoceramide, one of three major sphingolipids in yeast
physiological function
undifferentiated and differentiated Neuro2a cells are protected from mechanical, heat (42°C) and oxidative stress by nimodipine, or at least to a lower extent by nifedipine. Higher expression of enzyme FA2H induced by nimodipine may cause higher survival of Neuro2a cells stressed with surgery-like stressors
additional information
important role of the dimetal-binding histidines in catalysis, residues Tyr322 and Asp323 are critical determinants involved in the hydroxylase reaction. Molecular dynamics simulations, structure-function analysis, and generation of a model of ceramide binding to enzyme Scs7p
additional information
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important role of the dimetal-binding histidines in catalysis, residues Tyr322 and Asp323 are critical determinants involved in the hydroxylase reaction. Molecular dynamics simulations, structure-function analysis, and generation of a model of ceramide binding to enzyme Scs7p
